The largest physiological increments in glucose usage occur with muscular work. This appears to be, to some extent, due to an increase in the effectiveness of circulating insulin. However, other factors such as increased muscle blood flow and metabolic rate also seem to enhance glucose metabolism during exercise. The proposed experiments are aimed at elucidating the mechanisms involved in glucose uptake and metabolism during test exercise and recovery. Treadmill exercise in dogs, catheterized chronically for sampling across the hindlimb and the liver, will be our model for studying metabolism during muscular work. In addition, isotopic (3-3H glucose and U-14C-glucose) infusions will be used to assess glucose metabolism. In one set of experiments, circulating glucose levels will be held constant at one of four concentrations (90, 120, 150, or 180 mg/dl) while insulin levels will be fixed by an infusion of somatostatin with basal replacement of the hormone. These protocols will establish the relationship between glycemia and peripheral glucose uptake and metabolism in the face of constant insulin levels. In a second series of experiments an insulin infusion will be held constant at one of four different rates (0.5, 1.0, 2.0, and 15.0 mU/kg-min) while euglycemia will be maintained with an exogenous glucose infusion. These experiments should enable us to determine whether the enhanced insulin action seen during exercise is due to a change in the responsiveness and/or the sensitivity to this hormone.